COVID Drug Paxlovid Interacts With Widely Used CV Meds: Review

The antiviral treatment combining nirmatrelvir and ritonavir (Paxlovid; Pfizer), though effective for patients with mild-to-moderate COVID-19, can interact with many commonly prescribed cardiovascular medications, researchers highlight in a review in the Journal of the American College of Cardiology.

The main culprit is ritonavir, which was first approved for the treatment of HIV in 1996 and affects both the CYP450 pathway involved in the metabolism of many medications and the P-glycoprotein pump involved in drug transport.

“The clinical community should be aware that there is a potential for serious interaction when Paxlovid is prescribed for people on cardiovascular medications,” Sarju Ganatra, MD (Lahey Hospital and Medical Center, Beth Israel Lahey Health, Burlington, MA), senior author of the review, told TCTMD. “Having said that, it’s not a reason to deter people from prescribing Paxlovid.”

The paper includes a table and a figure listing dozens of CV medications and whether Paxlovid is safe to use in combination, whether some type of adjustment or temporary interruption of the CV medication is required before use of the antiviral therapy, or whether Paxlovid shouldn’t be used at all. The central illustration contains an algorithm to help guide clinicians through this decision-making process.

“In most cases, our attempt has been that if it is practically feasible, we would suggest a pathway where if any modification is needed in the medication itself—whether it’s holding or reducing the dose—patients do get Paxlovid treatment,” Ganatra said.

But that’s not always possible, especially when patients are taking a CV medication with a long half-life, he noted. The antiarrhythmic amiodarone, for example, has a very long half-life, and even it were interrupted, it would remain the system for long enough to make Paxlovid treatment impractical. “In those scenarios, we have suggested an alternative treatment for COVID-19, which I think is equally important to recognize for clinicians and patients—that sometimes holding a medication itself may not be enough to avoid interaction,” he explained.

The clinical community should be aware that there is a potential for serious interaction when Paxlovid is prescribed for people on cardiovascular medications. Sarju Ganatra

Paxlovid has been an exciting development in the response to the pandemic, Ganatra said. In the EPIC-HR trial, it was shown to reduce the risk of hospitalization or death by day 28 by 89% in high-risk, nonhospitalized, unvaccinated adults with COVID-19. The US Food and Drug Administration authorized the combination therapy for emergency use in December 2021, with an indication for nonhospitalized patients 12 and older with mild-to-moderate COVID-19 and a high risk for progression to severe disease.

Patients with CVD and CV risk factors were well represented among the high-risk patients and derived even greater benefits than the overall trial cohort. But many of these patients are taking medications that may interact in potentially harmful ways with Paxlovid.

Much of that is due to the inclusion of ritonavir, which was added to nirmatrelvir to delay hepatic metabolism and lengthen the amount of time its allowed to work in the body. Ritonavir inhibits enzymes of the CYP450 pathway, mainly CYP3A4 but also CYP2D6. These enzymes are involved in the metabolism of many drugs, including numerous medications used by patients with cardiovascular disease.

An FDA fact sheet on Paxlovid for healthcare providers goes into detail about potential drug-drug interactions that can lead to serious or life-threatening reactions, but the review in JACC, with lead author Sonu Abraham, MD (Lahey Hospital and Medical Center, Beth Israel Lahey Health), focuses on medications used in the setting of various cardiovascular diseases.

Some of the information on interactions is based on clinical data stemming from ritonavir’s use for HIV over the past few decades, whereas some is derived from what’s known about the drugs’ pharmacokinetics and pharmacodynamics.

To simplify the information, the authors provide a figure containing 80 medications across several categories: antiplatelets/anticoagulants, lipid-lowering agents, antianginals, antihypertensives, antiarrhythmics, heart failure therapies, pulmonary hypertension therapies, immunosuppressive agents, and anti-inflammatories. Those safe to coadminister with Paxlovid get a blue dot (36 drugs), those with a potential interaction requiring a dose adjustment or temporary discontinuation get an orange dot (34 drugs), and those that shouldn’t be used with Paxlovid get a grey dot (20 drugs).

Ganatra highlighted antiplatelets/anticoagulants, antiarrhythmics, and certain statins as major areas of concern when it comes to drug-drug interactions with Paxlovid because of the wide use of the medications. However, most interactions and serious consequences—which can include increases in bleeding, life-threatening arrhythmias, myopathy, or liver toxicity—can be avoided by either holding those drugs or reducing the dose, he said. “So there is a way around it and still people can get their desired COVID-19 treatment with Paxlovid.”

Immunosuppressive agents used in heart transplant recipients are not as commonly prescribed but potential interactions with Paxlovid that lead to toxic drug concentrations are of particular concern because of how sick the patients are, Ganatra said.

“The importance of medication reconciliation before initiation of nirmatrelvir/ritonavir cannot be overemphasized to avoid serious drug-drug interactions,” the authors write.

Ganatra pointed out that hospitals and healthcare systems are in a position to help address this issue by making adjustments to their electronic health records systems. Integrated algorithms, he noted, can warn prescribers about potential interactions and provide possible solutions.